chr7-100430158-C-T

Variant names:

• chr7-100430158-C-T
• rs1341381648
• NM_019606.6:c.140C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_019606.6(MEPCE):​c.140C>T​(p.Thr47Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000179 in 1,284,008 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: MEPCE NM_019606.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.61
• Publications: 0 publications found

Genes affected

MEPCE (HGNC:20247): (methylphosphate capping enzyme) Enables 7SK snRNA binding activity and RNA 5'-methyltransferase activity. Involved in RNA modification; positive regulation of protein localization to Cajal body; and positive regulation of snRNA transcription by RNA polymerase II. Located in nucleus. Part of 7SK snRNP. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000289690 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.11229569).
• BS2: High AC in GnomAdExome4 at 19 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019606.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEPCE	NM_019606.6	MANE Select	c.140C>T	p.Thr47Met	missense	Exon 1 of 4	NP_062552.2
	MEPCE	NM_001194990.2		c.-811-457C>T		intron	N/A	NP_001181919.1	Q7L2J0-2
	MEPCE	NM_001194991.2		c.-396-872C>T		intron	N/A	NP_001181920.1	Q7L2J0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEPCE	ENST00000310512.4	TSL:1 MANE Select	c.140C>T	p.Thr47Met	missense	Exon 1 of 4	ENSP00000308546.2	Q7L2J0-1
	ENSG00000289690	ENST00000695707.1		c.-396-872C>T		intron	N/A	ENSP00000512107.1
	MEPCE	ENST00000715739.1		c.140C>T	p.Thr47Met	missense	Exon 1 of 4	ENSP00000520510.1	Q7L2J0-1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152078 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000168 AC: 19 AN: 1131816 Hom.: 0 Cov.: 31 AF XY: 0.0000204 AC XY: 11 AN XY: 539708

African (AFR) AF: 0.00 AC: 0 AN: 23166

American (AMR) AF: 0.00 AC: 0 AN: 8798

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15364

East Asian (EAS) AF: 0.00 AC: 0 AN: 26668

South Asian (SAS) AF: 0.0000891 AC: 3 AN: 33654

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25584

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3504

European-Non Finnish (NFE) AF: 0.0000126 AC: 12 AN: 948894

Other (OTH) AF: 0.0000866 AC: 4 AN: 46184

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152192 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74408

African (AFR) AF: 0.00 AC: 0 AN: 41562

American (AMR) AF: 0.0000654 AC: 1 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5154

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67956

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.067	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.017
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		1.6
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.44	N
REVEL	Benign	0.054
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.038	D
Polyphen		0.78	P
Vest4		0.15
MutPred		0.15		Loss of phosphorylation at T47 (P = 0.0172)
MVP		0.16
MPC		1.8
ClinPred		0.89	D
GERP RS		5.2
PromoterAI		-0.099	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.15
gMVP		0.24
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1341381648; hg19: chr7-100027781; COSMIC: COSV60108676; COSMIC: COSV60108676;